Ubiquitin-activating enzyme

Enzyme that activates ubiquitin in the ubiquitination process

Ubiquitin-activating enzyme (E1) is a crucial enzyme in the process of ubiquitination, which is the attachment of ubiquitin to a substrate protein. This process is essential for various cellular functions, including protein degradation, cell cycle regulation, and DNA repair.

Structure

Ubiquitin-activating enzymes are characterized by their ability to bind ATP and ubiquitin. The enzyme has a catalytic cysteine residue that forms a thioester bond with ubiquitin. The structure of E1 is complex, involving multiple domains that facilitate its interaction with ATP and ubiquitin.

Ubiquitin-activating enzyme bound to ubiquitin.

Mechanism

The ubiquitin-activating enzyme initiates the ubiquitination process by catalyzing the adenylation of ubiquitin, which involves the binding of ATP and ubiquitin to form a ubiquitin-adenylate intermediate. This is followed by the transfer of ubiquitin to the active site cysteine of E1, forming a thioester bond.

Mechanism for the binding of ATP and then ubiquitin substrate to the ubiquitin-activating enzyme.

Function

E1 enzymes are responsible for the activation of ubiquitin, which is then transferred to a ubiquitin-conjugating enzyme (E2). This activation is the first step in the ubiquitination cascade, which ultimately leads to the attachment of ubiquitin to target proteins. This process is vital for the regulation of protein turnover and cellular homeostasis.

Active Site

The active site of the ubiquitin-activating enzyme contains a cysteine residue that is crucial for its catalytic activity. This cysteine forms a transient thioester bond with ubiquitin, facilitating its transfer to E2 enzymes.

Cysteine highlighted in the active site of ubiquitin-activating enzyme.

Role in Ubiquitination

Ubiquitination is a post-translational modification that tags proteins for degradation by the proteasome. The ubiquitin-activating enzyme is the first enzyme in the ubiquitination pathway, playing a pivotal role in the regulation of protein levels within the cell.

Diagram of the ubiquitylation process.

Related pages

• Ubiquitin-conjugating enzyme
• Ubiquitin ligase
• Proteasome

References

• Hershko, A., & Ciechanover, A. (1998). The ubiquitin system. Annual Review of Biochemistry, 67, 425-479.
• Pickart, C. M. (2001). Mechanisms underlying ubiquitination. Annual Review of Biochemistry, 70, 503-533.

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  Ubiquitin-activating enzyme bound to Ubiquitin

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  Ubiquitin-activating enzyme bound to ATP and ubiquitin substrate

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  Ubiquitin activating enzyme cysteine highlighted

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  Cys and Arg active site of ubiquitin activating enzyme

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  Mechanism for the binding of ATP and then Ubiquitin substrate to the ubiquitin activating enzyme

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  Ubiquitylation